The long term goal of this project is to understand the neural basis of cortical function. We study the olfactory pathway, which consists of simple cortical structures processing a well-defined input, the information carried by odor molecules. Recent evidence is converging on a set of mechanisms underlying odor discrimination, which we will test in this grant. The initial interaction between odor molecules and odor receptors in the olfactory receptor neurons will be analyzed using patch recordings and Ca2+ imaging of cells isolated from parts of the olfactory epithelium that show heightened odor sensitivities, in both salamanders and rodents. Homologous series of odor compounds will be tested, and blockers of related neurotransmitter receptors will be used to dissect the responses pharmacologically. At the first stage Of synaptic processing, we will analyze the mapping of odor responses in the olfactory glomeruli using the voltage-sensitive dyes. This should further test the hypothesis that odor molecular structures are encoded as "odor images" in the glomeruli. in the olfactory bulb, mechanisms underlying synaptic processing of odor information will be analyzed using in vitro slices and cultured cells of rodents. Critical hypotheses will be tested regarding the roles of metabotropic glutamate receptors, GABAergic inhibitory mechanisms, and the cGMP/cyclic nucleotide gated channel system, in sensory processing and olfactory memory. The results should add to a growing consensus on the molecular and neural mechanisms underlying the sense of smell. This will provide a better scientific basis for understanding normal smell perception as well as disorders of smell perception and memory in neurological disease.